The role of polo-like kinase 1 in the inhibition of centrosome separation after ionizing radiation

doi:10.1074/jbc.M505450200

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Papers In Press, published online ahead of print September 12, 2005
J. Biol. Chem, 10.1074/jbc.M505450200
Submitted on May 18, 2005
Revised on September 1, 2005
Accepted on September 12, 2005

The role of polo-like kinase 1 in the inhibition of centrosome separation after ionizing radiation

Wei Zhang, Lynda Fletcher, and Ruth J Muschel

Radiation Oncology and Biology, Univ. of Oxford, Oxford OX3 9DU

Corresponding Author: weizhang7{at}yahoo.com

Activation of the G2/M cell cycle checkpoint by DNA damage prevents cells from entering mitosis. Centrosome separation is initiated in G2 phase and completed in M phase. This critical process for cell division is targeted by G2/M checkpoint. Here we show that Plk1 signaling plays an important role in regulation of centrosome separation after DNA damage. Constitutively active Plk1 overrides the inhibition of centrosome separation induced by DNA damage. This inhibition is dependent on ATM, but not on Chk2 or Chk1. Nek2 is a key regulator of centrosome separation and is a target of Plk1 in blocking centrosome separation. We found that Plk1 can phosphorylate Nek2 in vitro and interacts with Nek2 in vivo. Downregulation of Plk1 with RNAi prevents Nek2 induced centrosome splitting. DNA damage is known to inhibit Plk1 activity. We propose that the DNA damage induced inhibition of Plk1 leads to inhibition of Nek2 activity and thus prevents centrosome separation.

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